Intraventricular hemorrhage continues to be a common occurrence in the neonate, with a high incidence of permanent neurologic deficits in the survivors. Although many previous studies have attempted to identify its etiology, relatively little is known regarding the functional status of the cerebral vasculature following its exposure to extravascular blood. Extensive clinical and experimental studies in the adult indicate that cerebral vasospasm and related impairments in cerebrovascular reactivity result from blood in the subarachnoid space, and this vascular dysfunction, in turn, leads to secondary ischemic injury. In addition, it appears that vascular endothelial cell injury secondary to extravascular blood exposure may be a primary cause of such dysfunction, underscoring the importance of endothelium-derived vasoactive products such as nitric oxide in the control of cerebral blood flow. We hypothesize that (1) vasospasm occurs in neonate cerebral arteries following prolonged exposure to extravascular blood; (2) that ischemic injury results in brain regions served by the vasospastic vasculature, and (3) that blood-induced impairments in nitric oxide-based mechanisms of vascular regulation contribute to cerebrovascular dysfunction and brain injury in the neonate. In the majority of infants suffering intraventricular hemorrhage, blood entering the lateral ventricles spreads throughout the ventricular system and collects in the posterior fossa; thus, the posterior circulation of these babies is typically exposed to blood. We will therefore use a clival window in newborn pigs to provide experimental access to the posterior circulation so that we can determine the delayed effects of intracisternally injected blood on the reactivity of these vessels. Blood-induced vasospasm of the basilar artery will be documented by morphometric analyses of arterial cross sections, and ischemic injury of the posterior fossa structures will be analyzed histochemically and histologically. Vascular reactivity to physiologic and pharmacologic stimuli that induce vasodilation via nitric oxide will be quantified by fluorescein videomicroscopy and hydrogen clearance. These studies will be the first in a neonate model to systematically examine cerebrovascular reactivity secondary to intraventricular hemorrhage.
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